title: MEK/ERKs signaling is essential for lithium-induced neurite outgrowth in N2a cells.
abstract: Lithium, a drug used for the treatment of bipolar disorder, has been shown to affect different aspects of neuronal development such as neuritogenesis, neurogenesis and survival. The underlying mechanism responsible for lithium's influence on neuronal development, however, still remains to be elucidated. In the present study, we demonstrate that lithium increases the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt) and promotes neurite outgrowth in mouse N2a neuroblastoma cells (N2a). The inactivation of mitogen-activated protein kinase kinase (MEK)/ERKs signaling with a MEK inhibitor inhibits neurite outgrowth, but it enhances Akt activation in lithium-treated N2a cells. Furthermore, the inactivation of phosphoinositide-3-kinase (PI3K)/Akt signaling with a PI3K inhibitor increases both lithium-induced ERKs activation and lithium-induced neurite outgrowth. Taken together, our study suggests that lithium-induced neurite outgrowth in N2a cells is regulated by cross-talk between the MEK/ERKs and PI3K/Akt pathways and requires the activation of the MEK/ERKs signaling.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, China.
authors.forename: Zhuyao
authors.initials: Z
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Yao
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Yunlin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Guoxian
authors.initials: G
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018692:Antimanic Agents; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018021:Lithium Chloride